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Chapter 20 - Molecular Diagnostics in Bone Marrow Haematopathology

Published online by Cambridge University Press:  12 November 2020

Jon van der Walt ,
Attilio Orazi  and
Daniel A. Arber
By
Mats Ehinger ,
Per Levéen  and
Anna Porwit
Jon van der Walt
Affiliation:
St Thomas’ Hospital, London
Attilio Orazi
Affiliation:
Texas Tech University
Daniel A. Arber
Affiliation:
University of Chicago
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Summary

Molecular diagnostics, i.e. the detection and analysis of disease-related changes of DNA or RNA, is becoming ever more important for the diagnosis of bone marrow (BM) neoplasms. In modern BM haematopathology, molecular diagnostics should always be part of an integrated diagnostic approach including clinical information, morphology and immunophenotyping. It is the responsibility of the haematopathologist to interpret the information gathered and to produce a final diagnosis. For this purpose, the practising haematopathologist must be familiar with the various molecular techniques needed and possess an in-depth knowledge of their applications for the diagnosis of BM neoplasms. The first part of this chapter focuses on the most important molecular techniques currently used in everyday diagnostics in the modern haematopathological laboratory. The second part highlights the major molecular and genetic aberrations of diagnostic value across the different haematological disease entities. Ideally the haematopathological laboratory should either be able to perform the relevant tests or be in close cooperation with a laboratory performing them for optimal diagnostics. Such cooperations also include multidisciplinary conferences, where clinicians and haematopathologists meet to discuss the diagnoses of afflicted patients.

Keywords

Molecular diagnosticsDNARNAPCRRT-PCRNGSWGSWESFISH
Type
Chapter
Information
Diagnostic Bone Marrow Haematopathology , pp. 362 - 417
Publisher: Cambridge University Press
Print publication year: 2021

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References

Swerdlow, SH, Campo, E, Harris, NL (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2016.Google Scholar
Kallioniemi, A, Kallioniemi, OP, Sudar, D, et al. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 1992;258(5083):818–21.CrossRefGoogle ScholarPubMed
Sato-Otsubo, A, Sanada, M, Ogawa, S. Single-nucleotide polymorphism array karyotyping in clinical practice: where, when, and how? Semin Oncol. 2012;39(1):13–25.CrossRefGoogle ScholarPubMed
Tong, Y, Shen, SZ, Jiang, H, Chen, Z. Application of digital PCR in detecting human diseases associated gene mutation. Cell Physiol Biochem. 2017;43(4):1718–30.Google Scholar
Schena, M, Shalon, D, Davis, RW, Brown, PO. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science. 1995;270(5235):467–70.CrossRefGoogle ScholarPubMed
Han, Y, Gao, S, Muegge, K, Zhang, W, Zhou, B. Advanced applications of RNA sequencing and challenges. Bioinform Biol Insights. 2015;9(Suppl 1):29–46.Google Scholar
Tsang, HF, Xue, VW, Koh, SP, et al. NanoString, a novel digital color-coded barcode technology: current and future applications in molecular diagnostics. Expert Rev Mol Diagn. 2017;17(1):95–103.Google Scholar
Lister, R, Pelizzola, M, Dowen, RH, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462(7271):315–22.CrossRefGoogle ScholarPubMed
Saiki, RK, Bugawan, TL, Horn, GT, Mullis, KB, Erlich, HA. Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature. 1986;324(6093):163–6.CrossRefGoogle ScholarPubMed
Saiki, RK, Gelfand, DH, Stoffel, S, et al. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988;239(4839):487–91.CrossRefGoogle ScholarPubMed
Higuchi, R, Fockler, C, Dollinger, G, Watson, R. Kinetic PCR analysis: real-time monitoring of DNA amplification reactions. Biotechnology. 1993;11(9):1026–30.Google ScholarPubMed
Sanger, F, Coulson, AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol. 1975;94(3):441–8.CrossRefGoogle ScholarPubMed
Metzker, ML. Sequencing technologies: the next generation. Nat Rev Genet. 2010;11(1):31–46.Google Scholar
Dadi, S, Le Noir, S, Asnafi, V, Beldjord, K, Macintyre, EA. Normal and pathological V(D)J recombination: contribution to the understanding of human lymphoid malignancies. Adv Exp Med Biol. 2009;650:180–94.Google Scholar
van Dongen, JJ, Langerak, AW, Bruggemann, M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98–3936. Leukemia. 2003;17(12):2257–317.CrossRefGoogle ScholarPubMed
Hayes, SM, Love, PE. Strength of signal: a fundamental mechanism for cell fate specification. Immunol Rev. 2006;209:170–5.Google Scholar
Keim, C, Kazadi, D, Rothschild, G, Basu, U. Regulation of AID, the B-cell genome mutator. Genes Dev. 2013;27(1):1–17.CrossRefGoogle ScholarPubMed
Blom, B, Verschuren, MC, Heemskerk, MH, et al. TCR gene rearrangements and expression of the pre-T cell receptor complex during human T-cell differentiation. Blood. 1999;93(9):3033–43.Google Scholar
Starr, TK, Jameson, SC, Hogquist, KA. Positive and negative selection of T cells. Annu Rev Immunol. 2003;21:139–76.Google Scholar
van Krieken, JH, Langerak, AW, Macintyre, EA, et al. Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98–3936. Leukemia. 2007;21(2):201–6.CrossRefGoogle ScholarPubMed
Langerak, AW, van Dongen, JM. Multiple clonal Ig/TCR products: implications for interpretation of clonality findings. J Hematopathol. 2012;5:35–43.Google Scholar
Langerak, AW, Groenen, PJ, Bruggemann, M, et al. EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations. Leukemia. 2012;26(10):2159–71.CrossRefGoogle ScholarPubMed
Groenen, PJ, Langerak, AW, van Dongen, JJ, van Krieken, JH. Pitfalls in TCR gene clonality testing: teaching cases. J Hematop. 2008;1(2):97–109.Google Scholar
Lenze, D, Muller, H, Hummel, M. Considerations for the use of formalin-fixed and paraffin-embedded tissue specimens for clonality analysis. J Hematop. 2012;5:27–34.Google Scholar
Langerak, AW, Groenen, PJ, Jm van Krieken, JH, van Dongen, JJ. Immunoglobulin/T-cell receptor clonality diagnostics. Expert Opin Med Diagn. 2007;1(4):451–61.CrossRefGoogle ScholarPubMed
Vargas, RL, Felgar, RE, Rothberg, PG. Detection of clonality in lymphoproliferations using PCR of the antigen receptor genes: does size matter? Leuk Res. 2008;32(2):335–8.Google Scholar
Cancer Genome Atlas Research Network, Ley, TJ, Miller, C, Ding, L, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74.Google Scholar
Papaemmanuil, E, Dohner, H, Campbell, PJ. Genomic classification in acute myeloid leukemia. N Engl J Med. 2016;375(9):900–1.Google ScholarPubMed
Grimwade, D, Ivey, A, Huntly, BJ. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood. 2016;127(1):29–41.CrossRefGoogle ScholarPubMed
Bullinger, L, Dohner, K, Dohner, H. Genomics of acute myeloid leukemia diagnosis and pathways. J Clin Oncol. 2017;35(9):934–46.Google Scholar
Yohe, S. Molecular genetic markers in acute myeloid leukemia. J Clin Med. 2015;4(3):460–78.CrossRefGoogle ScholarPubMed
Dohner, H, Weisdorf, DJ, Bloomfield, CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136–52.Google Scholar
Nybakken, GE, Bagg, A. The genetic basis and expanding role of molecular analysis in the diagnosis, prognosis, and therapeutic design for myelodysplastic syndromes. J Mol Diagn. 2014;16(2):145–58.CrossRefGoogle ScholarPubMed
Bejar, R. Myelodysplastic syndromes diagnosis: what is the role of molecular testing? Curr Hematol Malig Rep. 2015;10(3):282–91.Google Scholar
Xie, M, Lu, C, Wang, J, et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med. 2014;20(12):1472–8.CrossRefGoogle ScholarPubMed
Genovese, G, Kahler, AK, Handsaker, RE, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371(26):2477–87.CrossRefGoogle ScholarPubMed
Jaiswal, S, Fontanillas, P, Flannick, J, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371(26):2488–98.Google Scholar
Delic, S, Rose, D, Kern, W, et al. Application of an NGS-based 28-gene panel in myeloproliferative neoplasms reveals distinct mutation patterns in essential thrombocythaemia, primary myelofibrosis and polycythaemia vera. Br J Haematol. 2016;175(3):419–26.Google Scholar
Ronaghi, M, Nygren, M, Lundeberg, J, Nyren, P. Analyses of secondary structures in DNA by pyrosequencing. Anal Biochem. 1999;267(1):65–71.Google Scholar

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